Decreased Number and Impaired Angiogenic Function of Endothelial Progenitor Cells in Patients with Chronic Renal Failure

BACKGROUND AND OBJECTIVES: The increased risk of cardiovascular disease in patients with chronic renal failure (CRF) has been explained by accelerated atherosclerosis and impaired angiogenesis, where endothelial progenitor cells (EPC) may play key roles. It was hypothesized that : "an altered EPC biology may contribute to the pathophysiology of CRF". SUBJECTS AND METHODS: EPC were isolated from CRF patients on maintenance hemodialysis (n=44) and from a normal control group (n=30). After morphological and immunological characterization, the number and in vitro angiogenic function of the EPC were evaluated. RESULTS: CRF patients showed markedly decreased numbers of EPC (44.6%) and colonies (75.3%) compared to the controls (p<0.001). These findings were corroborated by a 30.5% decrease in the migratory function in response to vascular endothelial growth factor (VEGF)(p=0.040) and by a 48.8% decrease in EPC incorporation into human umbilical vein endothelial cells (HUVEC)(p<0.001). In addition, The Framingham's risk factor scores of both the CRF (r=-0.461, p=0.010) and normal groups (r=-0.367, p=0.016) were significantly correlated with the numbers of EPC. Indeed, under the same burden of risk factors the number of circulating EPC was significantly lower in CRF patients than in the normal group (p<0.001). A significant correlation was also observed between the dialysis dose (Kt/V) and EPC incorporation into the HUVEC (r=0.427, p=0.004). CONCLUSION: The EPC biology, which is critical for neovascularization and the maintenance of vascular function, was altered in CRF. Our data strongly suggest that dysfunction of circulating EPC has a role in the progression of cardiovascular disease in patients with CRF.

Safety of One-Day Admission Transradial Coronary Intervention

BACKGROUND: Recent advances of percutaneous coronary intervention (PCI) and transradial coronary intervention (TRI) have made it possible to reduce the local complication rate and the time until a return to ambulation. The aim of this study is to assess the safety and the patient satisfaction of the TRI-based one-day admission program for PCI. METHODS: Total 230 consecutive patients underwent TRI on the day of admission, according to pre-determined inclusion criteria, from May 2001 to October 2003. The subjects were examined for clinical and angiographic characteristics. The patients having a same-day discharge were telephone-interviewed one day and seven days after discharge to assess late complications and the patients' satisfaction. RESULTS: The mean age of the subjects was 59+/-9 years and 77.4% were male patients. 169 (73.4%) had stable angina and 37 (16.1%) had unstable angina. Stents were implanted in 178 cases (69.3%). Of the 230 patients who underwent TRI, 206 patients (89.6%) could discharge on the same day after the procedure. The procedure was successful in 98.5%. The average hospital stay for them was 9.4+/-1.4 hours. Two subjects reported hematoma near the puncture site within 24 hours after discharge, and one reported this problem 7 days after discharge. During the follow-up, there were no cases reporting chest pain needing rehospitalization or such complications as subacute vessel closure. No deaths, myocardial infarctions or revascularization were noted during the follow-up period. The majority of the patients (n=197, 95.6%) were satisfied with the same-day admission and discharge. CONCLUSIONS: Same day admission and discharge after TRI seems to be safe as well as satisfactory for not low-risk patients.

Effect of Estrogen Replacement on Vascular Responsiveness in Ovariectomized Spontaneously Hypertensive Rat

BACKGROUND: Although postmenopausal estrogen replacement therapy is known to reduce cardiovascular mortality, the mechanism is not clear yet. Furthermore, the effect of estrogen on vascular tonus is reportedly variable according to the animal models, vascular beds and agonists used. MATERIALS AND METHOD: Bilateral ovariectomies were performed in 12 week-old, 18 spontaneously hypertensive rats (SHR) and 18 normotensive Wistar-Kyoto rats (WKY). Rats were divided into three groups according to the dose of 17beta-estradiol (E 2 ) pellets implanted subcutaneously two weeks after ovariectomy: control (no implantation), low-dose (0.5 mg) and high-dose (5 mg) E 2 replacement group. Two weeks after pellet implantation, organ bath experiments were performed using descending thoracic aortae. For endothelium-dependent relaxation, acetylcholine (10(-9) -3x10(-6) M) was cumulatively added into the vessels precontracted with 10(-7) M norepinephrine (NE). For vasoconstrictor responses, cumulative concentration-contraction curves were constructed in quiescent vessels using NE (10(-9) -10(-5) M), U46619 (10(-9) -3x10(-6) M), endothelin-1 (10(-10) -10(-7) M). In addition, contraction to angiotensin II (10(-7) M) was also obtained. Serum 17beta-estradiol levels were measured by radioimmunoassay. Blood pressure was measured by tail-cuff method in some SHRs before ovariectomy and after placebo/E 2 replacement. RESULTS: Endothelium-dependent relaxation to acetylcholine was impaired in WKY treated with 5 mg E 2 (pIC 50 : control vs 5mg E 2 : 7.75+/-0.13 vs 7.27+/-0.16: n=6: p<0.05). No significant effect was noted in SHR. Contraction to angiotensin II was inhibited by low-dose E 2 in WKY and high-dose E 2 in SHR (% of the contraction to 60 mM KCl: WKY: control vs 0.5 mg E 2 : 39+/-5 vs 25+/-2: SHR: control vs 5 mg E 2 : 34+/-4 vs 22+/-2: n=6 and p<0.05 in WKY and SHR). In contrast, NE-induced contraction was enhanced by E 2 replacement (both low- and high-dose) in WKY and SHR (WKY: control vs 0.5 mg E 2 vs 5 mg E 2 : AUC: 280+/-24 vs 387+/-26 vs 374+/-25: maximal contraction: 137+/-8 vs 166+/-8 vs 162+/-3: pD 2 : 7.63+/-0.11 vs 8.17+/-0.13 vs 8.13+/-0.13: SHR: control vs 0.5 mg E 2 vs 5 mg E 2 : AUC: 265+/-17 vs 349+/-16 vs 406+/-19: maximal contraction: 152+/-6 vs 181+/-9 vs 203+/-16: pD 2 : 7.45+/-0.13 vs 7.91+/-0.08 vs 8.04+/-0.04: n=6 and p<0.05 between control and treated groups in WKY and SHR for all parameters). Contraction to U46619 was enhanced by E 2 replacement in SHR (control vs 0.5 mg E 2 : AUC: 478+/-30 vs 574+/-23: maximal contraction: 181+/-9 vs 230+/-10: n=6: p<0.05 for both parameters). Maximal contractile response to endothelin-1 was also enhanced in SHR (control vs 0.5 mg E 2 vs 5 mg E 2 : maximal contraction: 165+/-7 vs 189+/-7 vs 199+/-8: n=6 and p<0.05 between control and treated groups) but not in WKY. Blood pressure was not different between placebo and E 2- treated SHR (171+/-2 vs 174+/-4 mmHg). CONCLUSION: In WKY, chronic high-dose estrogen replacement impairs endothelium-dependent relaxation to acetylcholine.: low-dose estrogen replacement does not affect endothelium-dependent relaxation in SHR and WKY. Estrogen replacement enhances the contraction to most of the contractile agonists tested except angiotensin II in both WKY and SHR. These results suggest that estrogen replacement affect the vascular tonus differently according to the vasoactive substances and/or hormones without significant effect on blood pressure.

Estrogen affects vascular tone differently according to vasoactive substances in ovariectomized Sprague-Dawley rat

The favorable effects of estrogen on cardiovascular diseases can be explained by several mechanisms such as changes in serum lipid profiles and thrombogenecity. Estrogen also affects the vascular tone, but there has been no report in which the effect of estrogen was tested comprehensively for several vasoactive substances, especially after long-term administration. Two weeks after bilateral ovariectomy in 8-week old female Sprague-Dawley rats, placebo or 17 beta-estradiol (E2) pellets (0.5 mg; released over 3 weeks) were implanted subcutaneously. Two weeks after pellet implantation, organ chamber experiments were performed using aortae. Compared with control, E2-treated vessels showed impaired endothelium-dependent relaxation to acetylcholine. E2 enhanced the contraction to norepinephrine and U46619 and had no effect on endothelin-1-induced contraction. In contrast, the contraction to angiotensin (AT)-II was inhibited by E2. Northern blot analysis for AT1 receptor expression using cultured aortic smooth muscle cells showed no difference between control and E2-treated cells, suggesting that AT1 receptor downregulation is not the likely mechanism. These results suggest that E2 affects the vascular tone variably according to vasoactive substances.

Evaluation of Left Ventricular Diastolic Function Using New Doppler Time Index

BACKGROUND: There is a clinical need for a simpler measurement of global cardiac function incorporating elements of both systole and diastole. Doppler time index is theoretically regarded as a sensitive index of global left ventricular perfomance and defined as the sum of isovolumetric contraction time (IVCT) and isovolumetric relaxation time (IVRT) divided by ejection time (ET). This study was designed to determine the clinical usefulness of the Doppler time index in patients with left ventricular diastolic dysfunction as well as systolic dysfunction. METHODS: The study population consisted of 23 patients with hypertension as a diastolic dysfunction group, 16 patients with low ejection fraction as a systolic dysfunction group and 31 subjects with normal LV function. The ejection fraction (EF) was measured using M-mode echocardiography. Doppler profiles such as IVCT, IVRT and ET were obtained from Doppler echocardiography. The Doppler time index [ (IVCT+RT)/ET] was calculated from each Doppler velocity profiles. RESULTS: IVRT, IVRT/ET and (IVCT+VRT)/ET were significantly increased in the diastolic dysfunction group (120.5+/-19.5 msec, 0.45+/-0.1, 0.64+/-0.2, respectively:p<0.001, p<0.001, p<0.001, respectively) compared with normal subjects (66.1+/-17.4 msec, 0.25+/-0.0, 0.41+/-0.1). IVCT and IVRT were significantly increased and ET was significantly shortened in systolic dysfunction group (75.4+/-25.7, 144.0+/-39.5 msec, 242.7+/-46.5 msec respectively:p<0.001, p<0.05, p<0.05, respectively) compared with diastolic dysfunction group (50.4+/-23.0 msec, 120.5+/-19.5 msec, 276.8+/-44.6 msec, respectively). IVCT/ET, IVRT/ET and (IVCT+IVRT)/ET also were increased in patients with systolic dysfunction group (0.32+/-0.1, 0.61+/-0.2, 0.93+/-0.2 respectively:p<0.01, p<0.01, p<0.001, res-pectively) compared with diastolic dysfunction group (0.19+/-0.1, 0.45+/-0.1, 0.64+/-0.2). Ejection fraction calculated by M-mode parameters was significantly correlated with (IVCT+IVRT)/ET (correlation coefficient - 0.605, p<0.001). CONCLUSION: The Doppler time index was significantly difficient from normal subjects in patients with isolated LV diastolic dysfunction as well as in those with systolic dysfunction. Thus, this index can be used as a sensitive indicator of myocardial performance.

Hemiazygos Continuation of Left Inferior Vena Cava Draining into the Right Atrium via Persistent Left Superior Vena Cava: A Variant of Polysplenia Syndrome Mimicking Aortic Dissection

We report a case of a 58 year-old male with polysplenia and left inferior vena cava draining into the right atrium via hemiazygous vein; the left superior vena cava and the coronary sinus in order. He presented dyspnea on exertion and atrial fibrillation. Originally, through findings of mediastinal widening in chest X-ray and the double lumen of the descending aorta in transesophageal echocardiography, he was erroneously diagnosed with aortic dissection. The anomalous venous connection was discovered via spiral CT and venography. We also found three to five small spleens via CT. We emphasize that normal left superior vena cava mimic aortic dissection on chest X-rays and transesophageal echocardiographys.

A Case of Rhabdomyolysis with Acute Renal Failure in the Course of Interferon Therapy for Chronic Active Hepatitis B / 대한신장학회잡지

Interferon has been tried as a drug of choice in patients with chronic active hepatitis by hepatitis B virus infection since Greenberg has reported the effectiveness of interferon in 1976. The effects of interferon therapy have been reported variably and various complications such as fever, myalgia, arthralgia, flu-like symptoms, temporary leukopenia and thrombocytopenia, alopecia, cardiovascular symptoms and autoimmune diseases have been reported. But rhabdomyolysis has been rarely reported in the interferon therapy of chronic hepatitis B. There were some cases of rhabdomyolysis with acute renal failure in the interferon therapy which was designed for chemotherapy of malignant melanoma and for chronic active hepatitis C virus infection. We reported a case of rhabdomyolysis with acute renal failure developed during the interferon therapy in a patient with chronic active hepatitis B.